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Objectives: In this study, we aimed to investigate the release and response of interleukin (IL)-18 to steroid treatment in a mouse model of allergic rhinitis., Methods: BALB/c mice were sensitized systemically by intraperitoneal injection of ovalbumin and locally by ovalbumin inhalation. Dexamethasone sodium phosphate was given by intraperitoneal injection in the steroid treatment group. Symptom scores, eosinophil counts, and IL-18 concentrations in the nasal and lung lavage fluids were analyzed., Results: The symptom scores and eosinophil counts of the negative control and steroid treatment groups were significantly lower than those of the positive control group (p < .01). The mean IL-18 concentrations in the nasal lavage fluid were not significantly different among the three groups (56.68 +/- 9.57,63.39 +/- 8.93, and 64.47 +/- 6.83 pg/mL, respectively). The IL-18 concentrations in the lung lavage fluid were significantly different between the positive control group and the steroid treatment group (430.75 +/- 154.54 and 69.94 +/- 14.26 pg/mL, respectively, p = .028)., Conclusions: The IL-18 concentration was found to be increased in the lung lavage fluid, but not in the nasal lavage fluid, in a mouse model of allergic rhinitis. Increased IL-18 concentrations returned toward the previous concentrations after steroid treatment. These results suggest that the roles of IL-18 may be different in the pathogenesis of allergic rhinitis and the pathogenesis of asthma.

Nitric oxide (NO), which is produced by nitric oxide synthase (NOS), has been recently identified as a multifunctional mediator. As for nasal tissue, however, the distribution and expression patterns of 3 isoforms of NOS, including neuronal NOS (nNOS, type I NOS), inducible NOS (iNOS, type II NOS), and endothelial NOS (eNOS, type III NOS), are still unclear. To evaluate the function of NO in the pathophysiology of nasal allergy, we investigated the distribution of NOSs in the nasal mucosa of C57BL/6 mice with allergic rhinitis to the house dust mite, Dermatophagoides farinae. Immunoreactivity to each isoform of NOS was immunohistochemically observed. In the allergic nasal mucosa, many eosinophils had infiltrated. Immunoreactivity to NOS types I and III was localized to the surface epithelial and vascular endothelial cells in both allergic and control groups without a statistically significant difference. In contrast, the type II NOS immunoreactivity was weak in normal mice and increased after allergic sensitization. The type II NOS expression of the surface epithelial and vascular endothelial cells was significantly elevated in the allergic group as compared with the control group. These findings suggest that a large amount of NO may be produced in the nasal mucosa of mice by type II NOS after allergic sensitization and that type II NOS may play an important role in the pathogenesis of allergic rhinitis.

This study aimed to determine the characteristics of ciliogenesis and the ciliary beat frequency (CBF) of cultured human nasal epithelial cells by means of an in vitro air-liquid interface (ALI) culture system. On the 14th, 21st, and 27th days of ALI culture, CBFs of cultured cells were measured with a video computerized analysis system, and the epithelial cell-collagen matrix complex was examined by scanning and transmission electron microscopy. Using a CBF distribution map, we calculated the proportion of ciliary beating area (CBA) on the cultured cells. On the 14th day, ciliated cells could be easily distinguished from other cells on scanning electron microscopy by their elongated cilia. Between the 14th and 27th days, the number of mature cilia increased, and after 27 days of air exposure, the cilia of each cell pointed to one direction. From the beginning of air-exposure culture until the 7th day, the number of secretory cells increased; however, from the 7th day to the 27th day, it decreased, and the number of ciliated cells increased. Total CBAs increased from the 7th day to the 21st day. The proportions of actively beating cells and the mean CBFs of beating cells among cultured epithelial cells increased with culture time. On the 21st day, the mean CBF of the cultured cells was similar to that of nasal ciliated cells in biopsy specimens (10.9 +/- 0.5 Hz versus 11.4 +/- 1.3 Hz), but until the 27th day, the CBF of cultured cells increased significantly (13.9 +/- 0.8 Hz). It is suggested that there may be some difference in CBF between nasal epithelial cells submitted to biopsy and nasal epithelial cells cultured by the ALI culture system.

Platelet activating factor (PAF), a potent chemical mediator in inflammation and allergic reaction, has been thought to induce mucociliary inhibition and epithelial damage in the airway mucosa. However, several recent papers have reported that PAF may not readily damage the airway epithelium. The aim of this study was to elucidate the pathogenesis of PAF-induced epithelial damage in terms of ultrastructural changes. Sixteen micrograms of PAF (1 mL of 16 microg/mL) was administered into the maxillary sinuses of rabbits. The rabbits were divided into 2 groups according to time intervals, and the antral mucosa was taken 1 and 3 days after administration of PAF. The tissue was processed for routine transmission electron microscopy. No epithelial degeneration was observed other than platelet aggregation, red blood cell stasis, and swelling of the endothelial cells 1 day after administration of PAF. Migration of inflammatory cells into the perivascular connective tissue, infiltration of eosinophils into the subepithelial and intraepithelial spaces, and vacuolar degeneration of the epithelial cells with focal loss of cilia were seen 3 days after administration of PAF. In conclusion, PAF induced infiltration of eosinophils into the epithelium, and resulted in epithelial degeneration that varied according to the time interval. Our findings suggest that PAF may cause epithelial damage through a series of secondary events, probably due to cytotoxicity of eosinophils infiltrating the epithelium.

Macrolide antibiotics have a variety of actions along with antimicrobial action. To determine the effects of oral administration of clarithromycin (CAM) on rheological properties, we measured the spinability, dynamic viscoelasticity, and solid composition of human nasal mucus from 18 patients with chronic sinusitis before and after administration of CAM for 4 weeks. After administration of CAM, the spinability and percent solid composition of nasal mucus increased from 26.5 +/- 12.2 mm to 40.2 +/- 18.7 mm and 7.86% +/- 3.47% to 13.90% +/- 3.67% (p < .05), respectively, whereas the ratio of the viscosity to the elasticity (eta'/G') of nasal mucus after the administration of CAM decreased in all of the mucus samples. These results suggest that treatment with CAM may modulate the rheological properties of nasal mucus in patients with chronic sinusitis.

Eosinophil-chemoattracting cytokines are thought to be important in the pathogenesis of allergic inflammation. However, little is known about the presence and significance of RANTES in nasal allergy and nasal polyps, two well-known rhinologic disorders characterized by eosinophil infiltration in the tissue. In order to evaluate the role of RANTES in eosinophil infiltration in vivo, the tissue distributions of RANTES and interleukin-5 (IL-5) and their correlation with eosinophil infiltration were investigated. Nasal mucosa specimens were obtained from 9 allergic and 12 control subjects, and nasal polyps from 6 allergic and 9 nonallergic subjects. All the subjects were divided into 4 groups: normal mucosa, allergic mucosa, nonallergic polyps, and allergic polyps. To identify the cellular localizations of RANTES and IL-5, we used specific immunohistochemical staining. We also investigated the differences in cytokine expression among the 4 groups, and the correlation between cytokine expression and eosinophil infiltration in the tissue. RANTES was expressed in the epithelium, endothelium, and some submucosal cells, while IL-5 was confined to the cells in the submucosa. Expression of both RANTES and IL-5 significantly increased in allergic mucosa and nasal polyps compared to normal mucosa; however, there was no significant difference in their expression between allergic and nonallergic polyps. Both cytokines had a significant correlation between their expression and either total or activated eosinophil numbers. The results of this study suggest that RANTES, as well as IL-5, plays a role in eosinophil recruitment in allergic nasal mucosa and nasal polyps in vivo.

Nasal polyps are the most common mass lesion of the nasal cavity. Various pathogenetic mechanisms have been proposed. However, the cause is still largely unknown, and treatment methods have not been changed for several hundred years. In order to investigate the role of cytokines in the pathogenesis of nasal polyps, expression of cytokine messenger RNAs (mRNAs) in nasal polyps was investigated. We performed reverse transcriptase-polymerase chain reaction and Southern blot to examine gene expression of the cytokines interleukin (IL)-1 beta, IL-6, IL-8, transforming growth factor (TGF)-beta, IL-4, IL-5, and interferon (IFN)-gamma and compared the results with the gene expressions of these cytokines in normal nasal mucosa. Nasal polyp tissues were obtained from 14 patients undergoing polypectomy for nasal obstruction. Among them, 4 patients suffered from associated perennial allergic rhinitis. The mRNAs of IL-4 and IL-5 (Th2 cytokines) as well as IFN-gamma (Th1 cytokine) were expressed in all of the nasal polyps obtained from the 14 patients, irrespective of the presence or absence of allergy, while 2, 0, and 4 of 6 normal turbinate mucosae expressed IL-4, IL-5, and IFN-gamma mRNAs, respectively. The mRNAs of IL-1 beta, IL-6, IL-8, and TGF-beta were expressed in 6, 1, 2, and 3 of 6 normal turbinate mucosae, respectively, while the mRNAs of these cytokines were expressed in all of the 14 polyp tissues except IL-6 mRNA, which was expressed in 13 nasal polyp tissues. There were no differences in the mean density ratios of each cytokine band on Southern blot between polyp tissues with allergy and those without allergy. These results suggest that many cytokines are produced in nasal polyps, that they may play important roles in the pathogenesis of nasal polyps, and that allergy per se may not play a fundamental role in the pathogenesis of nasal polyps.

To understand the role of cytokines in allergic nasal disease in humans, we designed this study to investigate the expression of cytokine mRNA in the nasal mucosa of 10 control subjects and 10 patients with perennial allergic rhinitis using a reverse transcription-polymerase chain reaction (RT-PCR) for IL-4, IL-5 (Th2 cytokines), and IFN-gamma (Th1 cytokine). Both IL-4 and IL-5 mRNAs were expressed in a significantly larger number of patients with allergic rhinitis than in control subjects. When the levels of expression of cytokines and beta-actin mRNA were quantitated, the mean density ratios (cytokine/beta-actin) for IL-4 and IL-5 were higher in patients with allergic rhinitis than in control subjects. In contrast, there were no differences in the number of subjects who showed expression of IFN-gamma mRNA, or in mean density ratios for IFN-gamma between the two groups. This study suggests that both IL-4 and IL-5 mRNAs are expressed almost universally in the nasal mucosa of patients with perennial allergic rhinitis during natural allergen exposure and also that Th2-type cytokines play a crucial role in the development of allergic nasal diseases in vivo.

To investigate the physiological role of substance P innervation (SPI) in the nasal mucosa from inhaled irritant macromolecules, SPI in the rat nasal mucosa was selectively stimulated with capsaicin and the degree of horseradish peroxidase (HRP) permeability across the nasal epithelium was evaluated by enzyme immunoassay or by histochemical electron microscopy. The serum level of HRP was reduced significantly in capsaicin-administered rats compared to control rats along the time course with quantitative analysis of the enzyme immunoassay. Control rats showed heavy permeation of HRP across the epithelium, but capsaicin-administered rats showed weak permeation of HRP across the epithelium with histochemical electron microscopy. The epithelial lining and its tight junctions were left intact as judged by electron microscopy. In conclusion, selective stimulation of SPI of the rat nasal mucosa with capsaicin decreased the epithelial absorption permeability to HRP without compromising the epithelial integrity. These findings imply that the physiological role of capsaicin-sensitive SPI in the rat mucosa is to protect the airway from inhaled irritant macromolecules.